Recent studies from our laboratory demonstrated a high degree of protection in mice immunized with ribosomes and ribosomal protein from yeast cells of Histoplasma capsulatum. We propose to characterize the immunogenic moiety in the ribosomal preparations from Histoplasma and to study the mechanism of the immune response, with the hope of developing a safe and effective vaccine against histoplasmosis. The protection elicited by immunization of mice with purified cytoplasmic and mitochondrial ribosomes, ribosomal RNA and protein from Histoplasma initially will be tested by i.v. challenge with yeast cells of H. capsulatum. In order to simulate the natural transmission of histoplasmosis a reliable procedure will be sought for the production of an infectious aerosol containing mycelial cells. The development of a reliable procedure would enable us to assess the immunoprotection elicited by ribosomal preparations following challenge of the immunized mice by the respiratory route. The physical and chemical characteristics of ribosomal preparations will be studied by a variety of techniques including sucrose density gradient centrifugation, ultracentrifugation, chromatography and disc gel electrophoresis. The role of lymphocytes, macrophages and hyperimmune serum in resistance to histoplasmosis will be studied to elucidate the nature of the immune response. BIBLIOGRAPHIC REFERENCES: Feit, C. and Tewari, R.P. 1974. Immunogenicity of ribosomal preparations from yeast cells of Histoplasma capsulatum. Infect. Immunity 10:1091. Tewari, R.P. 1975. Immunization against histoplasmosis. IN: E. Neter and F. Milgrom (eds.), The Immune System and Infectious Diseases. Proc. Fourth International Convocation on Immunology, p. 441. Buffalo, New York. S. Karger, Basel, Switzerland.